合成和评估具有潜在抗莱什曼尼性活性的混合硫胺 - 基化合物
Nathalia S de Oliveira1, Luana G de Souza1, Vitor M de Almeida2
1Laboratório de Catalise Orgânica, Instituto de Pesquisa de Produtos Naturais, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Archiv der Pharmazie
|December 4, 2023
概括
新的硫胺-合金杂交物对莱什曼亚马逊虫 (Leishmania amazonensis) 具有强烈的活性,这是导致莱什曼病的寄生虫. 有前途的化合物准了寄生虫的细胞性试素过氧化酶 (cTXNPx) 酶.
科学领域:
- 药用化学 医学化学
- 寄生虫学的寄生虫学
- 药物发现 药物发现 药物发现
背景情况:
- 莱什曼病是一种新兴的热带传染病,是由莱什曼病寄生虫引起的.
- 由于疾病的全球影响,开发新的治疗方法至关重要.
研究的目的:
- 合成和评估新型硫胺-化杂交物作为潜在的抗莱什曼病剂.
- 研究这些化合物的抗寄生虫活性和细胞毒性.
主要方法:
- 三甲氧和硫胺基分子的分子杂交.
- 合成了八种硫胺-化混合物,产量很高.
- 在体外测试对莱什曼亚马逊菌 (Leishmania amazonensis) 促生菌和细胞内促生菌.
- 对小鼠巨细胞的细胞毒性测定.
- 针对cTXNPx酶的分子对接和动力学模拟.
主要成果:
- 硫胺-混杂物表现出显著的抗莱什曼性活性 (IC50 = 1.72-3.19 μM).
- 三种化合物 (10c,10g,10h) 显示出对细胞内巨细胞的高活性,选择性指数高于9.
- 对接和分子动力学研究表明与向酶细胞类试素过氧化酶 (cTXNPx) 的相互作用.
- 预测的药物相似性和药物动力学特征是有利的.
结论:
- 新型的硫胺-合物混合物代表了利什曼病治疗的一类有前途的化合物.
- 化合物10c,10g和10h值得进一步研究,因为它们是候选物.
- 准cTXNPx酶是开发抗莱什曼病药物的可行策略.
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